The present invention generally relates to the field of enteral and parenteral nutritional formulations. More particularly, it relates to new and improved enantiomerically-enriched energy substrates for use in nutritional formulations providing high caloric density and low osmolarity which may also be used to beneficially direct intermediate metabolism in metabolically impaired patients.
Nutritional formulations are known which are used to supply the total nutritional needs of a patient. Other nutritional formulations are intended as supplements to provide certain special nutritional needs associated with various patient conditions and/or disease states. Most formulations include a protein component, a carbohydrate component and a lipid component.
The energetic and protein needs of patients having high metabolic activity are difficult to satisfy. Fats or lipids represent the richest nutrients from the point of view of energy. However, excessive consumption of fats presents a large number of health risks, especially cardiovascular health risks. Certain metabolic disorders involving lipids such as hyperlipidemia, obesity and diabetes also require restricted intake of fats generally, and saturated fats and cholesterol, in particular. The use of various substrates in nutritional formulations in above-normal quantities may induce metabolic perturbations and imbalances in the homeostasis of the patient.
It has been determined that not only the quantity but also the component makeup of the lipid fraction of a nutritional formulation may be very important for patients suffering from certain disease states or recovering from surgery, chemotherapy or traumatic injury. For example, hypernutrition for patients with respiratory failure may be a problem. Long chain triglycerides (LCTS) should be avoided during sepsis. Patients with insulin resistance should have their glucose requirements carefully regulated. The formulations, depending on their chemical composition, may also cause intestinal transit problems leading to diarrhea.
U.S. Pat. No. 5,283,260 to Miller, et al., describes the use of pyruvyl amino acid compounds, as alternative energy sources for the treatment of obesity and diabetes.
U.S. Pat. No. 5,283,260 to Galeb, et al., describe the use of low glucose-containing nutritional formulations for head trauma patients based on n-6 and n-3 fatty acids as alternative energy sources.
Hermanson, et al. in Acta Physiol. Scand., 1972, Vol. 86, pages 191-201, disclosed their findings that blood lactate appears to be metabolized by skeletal muscle in significant quantities rather than exclusively by the liver as was previously thought.
Jensen, et al., in Laboratory Investigation, Vol. 54, No. 5, page 574, 1986, describe a study which indicated that high lactate concentration encouraged macrophage cultures to secrete angiogenesis factors. Jensen, et al. concluded that high lactate concentrations may stimulate angiogenesis in wound healing. The authors also found that pyruvate did not cause the same response.
Stephanie Amiel, in Proceedings of the Nutrition Society, (1994), Vol. 54, pages 401-405, states that lactate studies suggest that lactate is able to support cerebral glucose metabolism and maintain cognitive functions during hypoglycemia. The author states that the development of therapeutic regimens to provide non-glucose fuels for cerebral metabolism during hypoglycemia needs to be more fully explored.
Maran, et al. in The Lancet, Vol. 343, Jan. 1, 1994, describe lactate as protective of brain function during hypoglycemia and recommend its therapeutic use in treating insulin dependent diabetes mellitus patients.
Some lipid components may be metabolized to form substrates whose concentration positively or negatively may affect the equilibria of other substrates. Moreover, many substrates may only be metabolized if present in a specific isomer form, such as (S)-(-) lactate, D-glucosides and the like. The presence of unhelpful and unusable substrates in nutritional formulations may lead to various problems including incomplete metabolism, toxic metabolites, side effects, and insufficient water solubility, to name but a few. It has been suggested that providing lactate may shift the equilibrium of the LDH enzyme catalyzed reaction: EQU Pyruvate+NADH+H.sup.+.fwdarw.lactate+NAD.sup.+
to the left, preventing or reducing the likelihood for developing lactic acidosis. Nutritional formulations having lipid fractions which comprise substantially only the useful enantiomeric forms of certain substrates and metabolites are generally not known.